Administration of prostaglandins to a wide variety of mucosal surfaces has resulted in alteration of the absorption or secretory functions of the mucosal cells. Similarly, the prostaglandins have been found to produce alterations in the secretory response produced by hormone stimulation of a variety of exocrine organs. Because of the wide variety of tissues affected by prostaglandins it has been hypothesized that they alter a common cellular entity. The effects of many hormones have been found to be mediated by the cell membrane messenger system adenyl cyclase, cyclic-AMP. Prostaglandins have been shown to alter cyclic AMP concentration in numerous tissues and exocrine organs. It is possible that the prostaglandins produce diverse effects by acting upon the biochemical system which controls the synthesis and breakdown of the important hormone intermediary, cyclic AMP. Stimulated by these concepts the principal investigator undertook preliminary investigations to determine if prostaglandins alter hepatic bile flow. The results of the studies suggest that the prostaglandins alter bile salt stimulated bile flow by producing a bicarbonate rich choleresis and also that the prostaglandins inhibit secretin stimulated bile flow. It is the purpose of this proposed research to determine if these effects are the result of prostaglandin produced changes in cyclic AMP metabolism. We intend to perform dose response experiments to confirm the findings noted above. To separate the prostaglandin induced systemic effects on bile flow from those produced by the drug itself, we intend to evaluate the effects of the prostaglandins on bile flow using the ex-vivo perfused liver. We propose to evaluate the effects of endogenous secretin release on bile prostaglandin and cyclic AMP levels to demonstrate the role these substances may play in hormone stimulated hepatic bile flow. It is anticipated that the proposed research will better define the cell membrane-intracellular mechanisms involved in the control of hepatic bile flow. Such information may lead to methods to better control the concentration of bile salts in hepatic bile.